DESCRIPTION (modified from the abstract): HHV-8 has been associated with all forms of Kaposi's sarcoma as well as other lymphoproliferative diseases. The mechanisms of disease development or progression are unknown, but it has been proposed the HHV-8 encoded cytokines may play an important role in the growth of KS and myeloma cells. This application will investigate the role of HHV-8 encoded IL-6 and three B-chemokine homologues (MIP-1a, b, BCK) as mitogenic stimuli for the proliferation of KS and myeloma cells. This investigation will be accomplished by: (1) determining the pattern of expression of vIL-6 and vchemokines in KS cells and in-vitro passaged BCBL cells, (2) comparing the functional activities of the viral and cellular IL-6 and chemokines, (3) defining aspects of the signal transduction pathways of the viral IL-6 and chemokines, and (4) studying the in-vivo effects of vIL-6 and chemokines in a related murine herpesvirus by the use of recombinant viruses. Together these combined analyses will provide data to determine the functional profiles of the viral cytokines and their likely clinical relevance as mediators of HHV-8 associated malignancies.